[unreadable] The American Liver Foundation estimates that one in ten people has some form of liver disease and that 26,000 people die each year from liver disease. In the year 2000, 18,137 people were listed for liver transplantation, only 4,934 cadaveric donor liver transplants were made, and 1,636 patients died while awaiting transplant. A medical need for a treatment modality that can "bridge" patients to transplant or slow or reverse the progression of liver disease clearly exists. Even better would be a new standard of care treatment that can be easily employed by any hospital at early stages (Parson's encephalopathy grade 1 and 2) of liver failure that would retard or prevent progression to acute liver failure that requires OLTx. Bound solute dialysis (BSD), practiced heuristically by the MARS and Biologic-DT approaches, offers the potential of a new standard of care treatment modality. Improvements in such heuristic practice require a theoretical approach that encompasses the underlying thermodynamics and transport phenomena. Such an analysis indicates that BSD is both more robust and more easily employed than expected from the heuristic approaches practiced here-to-fore. Experimental observations follow the theoretical predictions. The objective of this research proposal is to expend upon the preliminary studies in order to define what is necessary to bring BSD to the status of an easily employed standard of care treatment for liver disease that can be practiced with minimal requirements by any hospital or clinic. This will be accomplished by expanding the theoretical approach to encompass other forms of BSD, experimental validation of modeling predictions, development of an animal model of chronic liver failure, and preclinical evaluation of the various modes of BSD with the animal model. [unreadable] [unreadable]